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OBJECTIVE To explore the effects of ADRB2 gene regulatory region polymorphism on the efficacy of short-acting beta 2 receptor agonists （SABA） in the treatment of acute asthma attack in children. METHODS A total of 127 children with acute mild to moderate bronchial asthma who received SABA treatment for 7 days in the General Hospital of Northern Theater Command from October 2016 to October 2020 were selected to detect their genotype distribution and compare the improvement of pulmonary functional indicators and curative effect among different genotypes. The effect of the high-order interaction of gene polymorphism on therapeutic effect was investigated. RESULTS Among 127 children， there were 80， 44 and 3 cases of TT， TA and AA types at locus rs2895795， 93， 32 and 2 cases of CC， CG and GG types at locus rs11168070， and 41， 64 and 22 cases of GG， GA and AA types at locus rs12654778， respectively， in accordance with Hardy-Weinberg equilibrium （P＞0.05）. After treatment， the improvement rate of the peak expiratory flow in percent predicted value （PEF%pred） and the improvement rate of the forced expiratory flow at 75% vital capacity in percent predicted value （FEF75%pred） in children with TA type were significantly lower than that of TT type at locus rs2895795 （P＜0.05）； the improvement rates of PEF%pred and FEF75%pred in children with CG type were significantly lower than that of CC type at locus rs11168070 （P＜0.05）； the improvement rates of PEF%pred in children with GA and AA type were significantly lower than that of GG type at locus rs12654778 （P＜0.05）. The differences in fractional exhaled nitric oxide before and after treatment were not statistically significant among different genotypes at each locus （P＞0.05）. The proportion of remarkable improvement of children with TT type at locus rs2895795 was 2.358 times that of children with TA+ AA type （P＜0.05）， and there was no significant effect of higher-order interaction of ADRB2 polymorphism on the efficacy in children with asthma （P＞0.05）. CONCLUSIONS Polymorphisms in the regulatory region of the ADRB2 gene in children with bronchial asthma are associated with the efficacy of SABA in the treatment of acute asthma attack in children. At locus rs2895795， rs11168070 and rs12654778， the improvement of lung function of children with wild-type is more obvious， and the efficacy of SABA treatment on children with TT type is better at locus rs2895795.
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Astrocyte elevated gene-1 (AEG-1) is a positive regulator of tumorigenesis in human cancer cells. Human AEG-1 gene is located in chromosome 8q22 having 12 exons/11 introns. Chromosome 8q22 is known to be a hot spot for genomic alterations in several cancerous cells involving HCC. The aim of the study was assess association between the negative regulatory region of AEG-1 promoter mutations and genetic susceptibility to hepatocellular carcinoma. The negative regulatory region of the human AEG-1 promoter was evaluated in a total of 50 Iranian hepatocellular carcinomas (HCC) patients. For investigating AEG-1 promoter polymorphisms the PCR-sequencing method was used. In this study was found two new mutation C>T (-633) and G>C (-660) in the patient group. But it was not revealed the statistically significant association between any mutations in this region of the AEG-1 promoter with HCC susceptibility. According to presented data, we can say that the negative regulatory region of the AEG-1 promoter mutations did not exihibit significant relevance with hepatocellular carcinoma. We recommend further studies on the efficacy of the AEG-1 promoter in therapeutic targeting of the HCC.
Resumo: O gene AEG-1 é um regulador positivo da tumorigênese em células cancerígenas humanas. O gene humano AEG-1 está localizado no cromossomo 8q22 com 12 exons/11 introns. O cromossomo 8q22 é conhecido por ser um hotspot para alterações genômicas em várias células cancerígenas que envolvem o CHC. O objetivo do estudo foi avaliar a associação entre a região reguladora negativa das mutações do promotor AEG-1 e a suscetibilidade genética ao carcinoma hepatocelular. A região reguladora negativa do promotor humano AEG-1 foi avaliada em um total de 50 pacientes iranianos com carcinomas hepatocelulares (CHC). Para investigar os polimorfismos do promotor AEG-1, utilizou-se o método de sequenciação por PCR. Neste estudo foram encontradas duas novas mutações C>T (-633) e G>C (-660) no grupo de pacientes. Mas não foi revelada a associação estatisticamente significante entre quaisquer mutações nessa região do promotor AEG-1 com suscetibilidade ao CHC. De acordo com os dados apresentados, podemos dizer que a região reguladora negativa das mutações do promotor AEG-1 não demonstrou relevância significativa com o carcinoma hepatocelular. Recomendamos estudos adicionais sobre a eficácia do promotor AEG-1 no direcionamento terapêutico do CHC.
Subject(s)
Patients , Astrocytes , Carcinoma, Hepatocellular , Genetic Predisposition to Disease , CarcinogenesisABSTRACT
Objective@#To investigate the relationship between the polymorphism of upstream regulatory region (URR) in human leukocyte antigen-G (HLA-G) gene and the pathogenesis of severe preeclampsia.@*Methods@#Thirty-nine gravidas with severe preeclampsia, who were admitted to the Third Affiliated Hospital of Zhengzhou University from October 2008 to March 2009, were enrolled as the case group. Another 43 healthy gravidas at the third trimester were chosen as the control group. All gravidas in both groups were Han nationality. URR polymorphism in HLA-G gene was detected by PCR sequencing. Allele frequencies and genotype frequencies of all single nucleotide polymorphisms (SNPs) were compared between the two groups.@*Results@#(1) Eight SNPs were detected between -1179 and -689 in HLA-G gene URR in Chinese Han pregnant women. (2) In the severe preeclampsia group, the genotype frequency of -964GG was 12.8% (5/39), which was significantly lower than the frequency of 37.2% (16/43) found in the control group (P=0.012). The allele frequency of -964G was also significantly lower in the severe preeclampsia group than in the control group [38.5% (30/78) vs 57.0% (49/86), P=0.018). (3) In the severe preeclampsia group, the genotype frequency of -716TT was 17.9% (7/39), which was significantly lower than the frequency of 41.9% (18/43) found in the control group (P=0.019). In the severe preeclampsia group, the allele frequency of -716T was 39.7% (31/78), which was also significantly lower than the frequency of 60.5% (52/86) found in the control group (P=0.008). (4) No significant differences were found in the allele or genotype frequencies of -1140A/T, -762C/T or -725C/G in HLA-G gene URR between the two groups (P>0.05).@*Conclusion@#Some of the SNPs in HLA-G gene URR are associated with the susceptibility of severe preeclampsia in Chinese Han gravidas. Pregnant women carrying -964G or -716T may have reduced risk of severe preeclampsia.
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Congenital heart disease is defined as a large group of structural and functional deficits that arise during cardiac embryogenesis,which poses serious threat to children's health.Genetic factors play an important role in the pathogenesis of congenital heart disease.Except for disease-related gene coding regions,recent research suggests that regulatory regions of these genes also participate in its occurrence.Regulatory elements include promoter,enhancer and attenuator,etc.This article reviews the relationship between the changes of these elements and the pathogenesis of congenital heart disease in order to better clarify the underlying mechanism and bring new ideas for clinical managements.
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Background and purpose:The incidence of cervical cancer is rather high in Xinjiang, which is closely associated with the infection of human papilloma virus type 16 (HPV-16). The purpose of this study was to analyze the variants and function of HPV-16 upstream regulatory region (URR) in the tissues of cervical cancer biopsies from Xinjiang.Methods:The DNAs were extracted from the tissues of cervical epithelial atypical hyperplasia (CIN) and cervical cancer biopsies. HPV-16URR segments were ampliifed by PCR. Based on the sequence analysis of the URR, the representativeURR variants were selected and cloned into pGL3-Basic. The recombinant plasmids were transfected into Vero cell lines respetively. Luciferase activity of transfected cells was detected 48 h after transfection. Results:Fifty-ifve HPV-16URR DNA fragments were obtained through PCR, and 44 mutations were found from the URR fragments. 4 of these mutations, including nt7192(G→T) , nt7433(- →T), nt7435 (C→G) and nt7863 (A→-) occurred in all sequences. The mutation at nt7520 (G→A) occurred in 54URR sequences, and the 39 other mutations were present in different samples. Based on the location and frequency of the mutations in theURR fragments, 9URR variants were selected and cloned into pGL3-Basic. Then the luciferase activity of the cells transfected with pGL3-URR plasmids was detected respectively. Promoter activity ofURR mutants from cervical cancer are significantly higher than that ofURR mutants from CIN (P<0.01). Promoter activity ofURR fragments from some cervical cancer was signiifcantly higher than that of theURR fragments from SiHa and Caski cells.Conclusion:Multiple mutations occurred in HPV-16URR of cervical cancer patients from Xinjiang. The promoter activity and carcinogenicity of some URR mutants have been enhanced.
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Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE) data: type 2 diabetes mellitus (DM), hypertension (HT), and coronary artery disease (CAD). We showed that epistatic single-nucleotide polymorphisms (SNPs) were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012), which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE). Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.
Subject(s)
Coronary Artery Disease , Deoxyribonuclease I , Diabetes Mellitus , Diabetes Mellitus, Type 2 , DNA , Gene Expression , Genome-Wide Association Study , Hypertension , Korea , Polymorphism, Single Nucleotide , Regulatory Sequences, Nucleic Acid , Transcription FactorsABSTRACT
The genome of a new SV40 strain(SV-IMB)isolated from a rhesus monkey was completely sequenced and compared with other isolates.The results showed that the whole genome contains 5246bp,and the average identity of SV-IMB was 98.1% as compared to other SV40 isolates.Its regulatory region is composed of a complete enhancer and a defective enhancer.Amino acid changes occurred to some extent in both the large T antigen (T-Ag) and VP1 region.The findings demonstrate that the SV-IMB is a new SV40 isolate.
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Objective To investigate the mechanisms of Mal gene down regulated in human esophageal cancer. Methods We amplified the 5′regulatory region of Mal gene in normal placenta tissue and human esophageal cancer cell lines EC9706、EC8712、EC109 by optimization the PCR methods, cloned and sequenced the PCR products and compare the sequence. Results Human esophageal cancer cell lines EC9706、EC8712、EC109 all have the 654 th of 5′regulatory region of Mal gene T to C changes, corresponding codon changed from TCC to CCC, and the amino acid which it codes changed from serine to proline; EC9706 also has the 657 th of 5′regulatory region of Mal gene T to C changes, corresponding codon changed from TGC to CGC, the amino acid which it codes changed from cysteine to arginine; EC8712 has the 139 th of 5′regulatory region of Mal gene A to G changed, corresponding codon changed from GGA to GGG, the amino acid which it codes remains glycine. Conclusion Our results suggested there are may point mutation in 5′ region of Mal gene in human esophageal cancer.